Effects of age on pharmcokinetics of a central nervous system drug were studied. Biodisposition of phenobarbital was examined in male, Fischer-344 rats of four different age groups, 3-4, 11-12, 23-24, and 32-34 months. The drug was administered intraperitoneally, either as a bolus or continuously from implanted osmotic minipumps. Plasma and brain concentrations were determined after extraction by gas chromatographic analysis with a nitrogen selective detector. Significantly higher plasma and brain concentrations were found in the older as compared to younger rats, due to a decreased apparent plasma clearance. Plasma concentrations were not directly predictive of brain concentrations, because the brain/plasma concentration ratio of the drug did not remain constant during aging. These studies are a first step to understanding of altered clinical responsivity to drugs in the elderly.